The interleukin-1β-mediated regulation of proenkephalin and opioid receptor messenger RNA in primary astrocyte-enriched cultures

doi:10.1016/S0306-4522(96)00669-0

Neuroscience

Volume 79, Issue 2, 12 May 1997, Pages 517-524

https://doi.org/10.1016/S0306-4522(96)00669-0 Get rights and content

Abstract

Opioids have been found to modulate the function of the immune system by regulating the biochemical and proliferative properties of its cellular components. The interaction of opioid and immune systems, however, is not unidirectional, but rather, bidirectional in nature. In the CNS, one cellular target of immune system activation is the astrocytes, glial cells known to synthesize proenkephalin. We have recently shown that these cells also express the messenger RNA transcripts for the opioid receptors μ, δ and κ, raising the question of the functional significance of this opioid peptide and the related receptors in the astrocytes. That is, why do astrocytes express proenkephalin and opioid receptors, and are these molecules responsive to a factor to which the astrocytes could be exposed in vivo? Furthermore, do these molecules respond to this factor in a region-specific fashion? In the present study, in order to characterize the astrocytic opioid response to an immune factor, we examined the concomitant regulation of μ, δ, κ and proenkephalin messenger RNAs by interleukin-1β (1 ng/ml =60 pM, 24 h) in primary astrocyte-enriched cultures derived from the rat (post-natal day 1–2) cortex, striatum, cerebellum, hippocampus and hypothalamus. Interleukin-1β treatment was found to increase by 55–75% the level of μ receptor messenger RNA in striatal, cerebellar and hippocampal cultures, but not in cultures derived from the cortex or hypothalamus. However, the cytokine had no effect on the level of δ receptor messenger RNA in any of the five cultures examined. In marked contrast to its stimulatory effects on μ receptor messenger RNA levels and its lack of an effect on δ receptor messenger RNA expression, interleukin-1β reduced to 10–30% of control levels the κ receptor messenger RNA levels in all cultures. Interleukin-1β had no effect on the level of proenkephalin messenger RNA in cortical, striatal, cerebellar and hypothalamic cultures, but did significantly decrease the expression of proenkephalin messenger RNA in hippocampal cultures to 40% of the control level. Therefore, interleukin-1β differentially regulated opioid receptor messenger RNA in astrocyte-enriched cultures in a manner dependent upon both the receptor type and the brain region from which the culture was derived. The cytokine also differentially regulated proenkephalin messenger RNA in a region-dependent fashion.

These findings suggest a capacity for astrocytes to differentially regulate opioid peptide and receptor messenger RNAs in response to an immune factor, supporting the potential existence of a novel immune-opioid system interaction in the CNS.

Section snippets

Chemicals

All chemicals, unless otherwise stated, were of reagent grade and were obtained from Sigma (St. Louis, MO).

Primary glial cell cultures

Primary glial cultures were established as described previously.[22](Note that in the generation of primary cell cultures, all animal procedures were conducted in accordance with the guidelines set forth by the National Institute of Health for the care and use of laboratory animals. Additionally, all efforts were made to keep animal stress, suffering and discomfort to a minimum, and to

Effects of interleukin-1β on opioid receptor mRNA levels

Following a 24 h treatment with IL-1β (1 ng/ml=60 pM), the level of μ receptor mRNA was found to be increased in astrocyte-enriched cultures established from the striatum, cerebellum and hippocampus (Fig. 1, Table 1). This increase, which represented an approximate 55–75% elevation above control μ receptor mRNA levels, was not observed in the cortical or hypothalamic astrocyte-enriched cultures. Therefore, IL-1β produced a differential up-regulation of μ receptor mRNA in these cultures, confirming

Conclusions

Although the physiological significance of an IL-1β-mediated regulation of the astroglial opioid peptide and receptor mRNAs is unknown, it is interesting to note that both IL-1β and opioids have been implicated in the modulation of cell proliferation in the CNS. CNS infection, trauma or injury has been shown to enhance IL-1β synthesis and secretion in various immune cells, neurons and astrocytes.13, 21The secreted IL-1β produces many effects, including the activation of astrocytes and the

Acknowledgements

This work was supported by NIDA (grants DA 02265 and DA 08920). Additionally, B.B.R. was supported by a post-doctoral fellowship from NIDA (grant T32 DA 07268-05).

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The interleukin-1β-mediated regulation of proenkephalin and opioid receptor messenger RNA in primary astrocyte-enriched cultures

Abstract

Section snippets

Chemicals

Primary glial cell cultures

Effects of interleukin-1β on opioid receptor mRNA levels

Conclusions

Acknowledgements

Trends Neurosci.

Biochem. biophys. Res. Commun.

Blood

Brain Res.

Brain Res.

Trends pharmac. Sci.

Molec. Brain Res.

Regul. Pept.

Brain Res.

Interleukin-1 binding sites on astrocytes

Neuroscience

Rapid release of multiple hormones from rat pituitaries perfused with recombinant interleukin-1

Life Sci.

Neuroendocrine, sympathetic and metabolic responses induced by interleukin-1

Neuroendocrinology

Corticotropin-releasing-factor-producing neurons in the rat activated by interleukin-1

Science

Release of multiple hormones by a direct action of interleukin-1 on pituitary cells

Science

Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones

Science

A molecular basis for bidirectional communication between the immune and neuroendocrine systems

Physiol. Rev.

Interleukin 1 and Interleukin 2 enhance proopiomelanocortin gene expression in pituitary cells

J. Immunol.